Tina M owns Rio, and when she suspected he had EPM she called her veterinarian, Dr. Dan. Dr. Dan worked with us and by the end of the consulting Tina told us he was eager for his next EPM case!
Rio’s signs were unthriftyness, sidewinding and his rear legs were weak. His tail pull test indicated hemi-paresis. He had complicating issues, his pasture was hilly, he had Cushings and he suffered with chronic laminitis. And now it was suspected that he had EPM.
We were confident Rio didn’t have EPM but it would be a few years before we developed tests to support our suspicions. When Dr. Dan spun Rio in a tight circle (as tight as his disease allowed) he didn’t show nystagmus (a vestibular sign*). Rio wasn’t depressed. We were exploring a new test at the time Rio’s case came across our desk, the lymphocyte proliferation assay, and his results indicated his disease wouldn’t progress. Dr. Dan’s treatment gave “amazing” results, that let Tina concentrate on the Cushings and laminitis issues. At our last check in with Tina, Rio was happily grazing in a large, hilly pasture without issue.
*vestibular signs, such as lateral eye movement after spinning in a circle indicate central nervous system disease.
EPM or sarcocystosis?
Classically, a horse with EPM has a wobbly gait and antibodies against S. neurona. Serum testing supports the diagnosis if specific assays are used. If non-specific assays are used you’ll need a cerebrospinal fluid (CSF tap). You will get a percent likelihood of EPM because your result was compared to the results of a handful of horses that had EPM. A negative serum test will rule out infection with S. neurona and EPM.
EPM is defined as parasites in the central nervous system (CNS). EPM is a different disease than sarcocystosis! Sarcocystosis is exposure to the S. neurona organism that produces serum antibodies. Sarcocystosis occurs in more than 80% of the horses in the United States! EPM is very rare.
Signs of sarcocystosis appear before EPM
S. neurona challenged horses showed signs before the onset of lameness or ataxia. The earliest signs in experimentally infected horses appeared at day 6 or 7 after infection. Seventeen days after infection is the earliest that antibodies were detected. The signs associated with EPM appeared at 30 days after exposure. Remember the signs of sarcocystosis occur at 6-7 days.
You may have noticed these early signs in your horse. Early signs are changes in how the horse behaves, weakness (most often stumbling is a sign of weakness), laying down more than usual. Dropping feed and a change in tail carriage are also early signs infection. These are signs that are seen before the parasite is taken into the brain or spinal cord, before EPM.
We recorded these subtle changes. Clinicians don’t see these signs because the horses aren’t referred to them until they show ataxia or lameness, but owners detect them.
Hear ye! Hear ye! Early signs are important!
We published observations in six cases in “Early signs of Equine Protozoal Myeloencephalitis” in The Journal of Applied Research in Veterinary Medicine, Vol 1, No 4, in the Fall of 2003. The original submission discussed 24 cases, but the paper was whittled down to 6 cases by our peer reviewers and the company that paid for the study. The company was testing ponazuril’s ability to prevent EPM, it was disturbing to them that treated horses showed early signs.
Six case reports allowed us to alert veterinarians to an important part of Sarcocystis infections. Spoiler alert: these signs are due to inflammation, innate immunity stimulated by the organism as the horse eliminates the infection.
More horses in controlled experiments
Over years, we analyzed the early signs in 70 horses with experimental infections, daily for 4 months. It was odd that all the infected horses showed early signs; surprisingly, signs appeared in the same order after infection. There must be something about the pathogenesis of sarcocystosis that is unrelated to direct parasite damage. What we saw was not random—but sequential, progressive, and consistent. And reversible. We think we know what is going on and you should too.
The syndrome is responsive to treatment
Our observations concern treatment-responsive cases. Rapidly responsive cases are those treated with agents that affect neuroinflammation. Treated with specific neuroinflammatory-targeting treatments, not NSAIDs, told us a lot. Putting these drugs on board before the infection, like the Bayer study tried with ponazuril, prevented early signs, unlike ponazuril. We looked at the genetics of the horse and also characterized the inflammatory responses. Important factors for owners are pre-existing conditions like Cushing’s or chronic laminitis. Chronic inflammatory conditions to consider are encysted parasites or hind-gut ulcers.
Background on how infection/inflammation progresses in field infections
The ingestion of S. neurona sporocysts, shed by the opossum, leads to a biphasic disease. The first phase is an acute, generalized infection resulting in seroconversion, followed by a chronic stage of inflammation. The parasites are eliminated, but the horse is stuck in a chronic inflammatory cycle and inflammation drives clinical signs of disease.
If there is no new exposure, most horses exit this innate response phase. However, some horses get stuck in a chronic inflammatory cycle. And other horses are chronically exposed from the environment. It is important to know the difference. Serotyping can tell you the difference.
In very rare cases, the parasite is transported to the brain or spinal cord causing encephalitis, this is EPM. The parasites are eliminated before the horse dies. The literature is full of citations where parasites are not found, only residual inflammation that is consistent with what may have been induced by the parasites.
Merozoites modify the host immune system within 72 hours after infection, this is disclosed by lymphocyte proliferation assays. A veterinary neurologist, blinded to infection status, not only detected the infection group accurately before day 30, but she was also able to predict which horses would become the most afflicted at the end of the experiment at 120 days! She was looking at results from lymphocyte stimulation assays. These data showed that the type and extent of the inflammatory response is what drives disease severity.
Early Signs, what to look for
We did see the occasional horse with signs within a day or two of infection. Usually, the first signs were noted at 6-7 days. Parasites replicate quickly, within hours, and we wondered why it took a week to see signs. Horses were mildly afflicted and the infections were progressive over time. It took a month to document ataxia—that is when we scheduled our blinded observers. In our studies, they missed seeing the early signs that we saw.
There were no cases in which the horses were asymptomatic before acute, or severe disease ensued. The most severe cases (unable to get up and some with seizures) showed mild signs that would not normally be associated with EPM, and this was long before the crisis— occurring in 3 months. These unusual signs were behavior changes or weakness associated with tripping, falling, or parked stance.
Additional early signs we monitored were dropping feed, drooling, paresis (lip, facial, eyelid), behavior change, weakness (increased time lying down), and a decreased response to slap test (laryngeal hemiplegia). We saw muscle wasting, limb paresis, and ataxia—but these signs were at 30 days or beyond, and associated with EPM.
The preponderance of horses showed changes that we could attribute to infection by day 14. Let me repeat, the early signs preceded ataxia and lameness in all the horses. There was not a correlation between severity of early signs and ultimate severity of ataxia. The association was duration of the signs. Also, we associated the presence signs and the results of the leukocyte stimulation assay with disease outcome.
Horses with persistent early signs had EPM by day 30. Significantly, some horses with early signs resolved and the disease in those horses was not as severe. Horses that continued to display early signs were the most severely afflicted by the end of our trials. It was the duration of the inflammatory cycle that predicted clinical outcome.
In this chart we show the onset of signs in 10 horses, five infections resulted in EPM. We published this work in the Canadian Journal of Veterinary Research in 2008. “Onset” indicates the first day signs were seen after challenge. “Ataxia” and “paresis” indicate the degree of the disease at the end of the trial (on a scale of 1-5). “Score” is the cumulative daily score for early signs. As you can see, the highest "scores" were seen in the horses that became most afflicted except in Horse 8.
Horse 1 2 3 4 5 6 7 8 9 10
Onset 52 6 13 6 11 6 83 6 12 6
Ataxia 0 3 0 3 3 0 0 1 0 2
Paresis 1 3 0 3 3 0 0 1 0 3
Score 35 472 14 610 442 12 13 217 5 228
We could already predict outcome by the higher scoring animals before day 30. In this study horses 1, 3, 6, 7, and 9 were vaccinated with recombinant SAG1. We saw some early, mild signs in these horses, but the signs resolved quickly. The vaccinated horses got an innate response to the parasites, that reaction then resolved. The vaccinated horses did not become ataxic. The implications of these observations are complicated and beyond this paper.
The message is that the animals showing a high cumulative score had EPM. The animals with a low score, the signs abated, these horses did not have EPM and never became ataxic.
Lots of parasites vs inflammation
Undoubtedly, inflammation is a hallmark of S. neurona sarcocystosis and EPM. Inflammation was due to the presence of the parasites and/or the immune reaction to them.
In our study, antibody was detected in conjunction with early signs. Eventual EPM was prevented by vaccination (prior to challenge) using a recombinant vaccine that was identical to the challenge organism’s phenotype. The vaccinated horses attained very high antibody titers.
Our data indicated that antibodies (humoral immunity) did not mediate the inflammatory reaction that induced the multifocal signs. If it had been antibody mediated, the vaccinated horses, the ones with the highest antibodies, would be the sickest. The presence of antibodies ameliorated the clinical signs of EPM in the animals. This is why we say don’t treat antibodies, we say treat disease. And this is another reason why we discourage prophylactic anti-protozoal drugs that have not been tested for this indication.
Predicting outcomes from the soapbox
In summary, horses with mild ataxia, toe dragging and any of the other multitudes of signs that prompt the horse owner and the veterinarian to suspect EPM should be tested for antibodies against S. neurona. We’d like you to suspect sarcocystosis first. If the horse is not depressed and not showing any vestibular signs along with the gait deficits, we are fairly sure you will have a good to great outcome with therapy. This is why we discourage prophylactic anti-protozoal drugs that have not been tested for prophylaxis. If you are using a prophylactic protocol be sure and understand the experiments and possible outcomes of the program. Following anecdotal evidence can harm your horse.
Horses with vestibular signs, a wobbly gait and moderate to severe depression, may have EPM. There may be parasites present in the CNS. These horses are severely weak and ataxic. These cases may respond to treatment, just not as quickly and not as completely. These cases often relapse.